摘要
目的:基于代谢组学探讨在脂多糖诱导下蒲参胶囊改善何首乌特异质肝损伤的代谢物变化及作用机制。方法:将SD大鼠10只作为正常对照组,50只在脂多糖(2.80 mg/g)诱导下建立特异质模型,分别为模型对照组、蒲参胶囊5.4、10.8 g/kg组、何首乌2.7、5.4 g/kg组,各组大鼠以15 mL/kg灌胃相应药物,5 h后尾静脉注射脂多糖,8 h后收集血清及肝组织,检测血浆丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)活力,白细胞介素1β(IL-1β)、γ干扰素(IFN-γ)含量,肝组织中超氧化物歧化酶(SOD)活力、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)含量及肝组织病理变化,用超高效液相色谱-四级杆-静电场轨道阱高分辨质谱法(UPLC-QE-Obritrap-MS)进行血浆代谢物及代谢通路分析。结果:与正常对照组相比,模型对照组大鼠血清ALT、AST活力均无显著变化,肝脏切片可见轻微炎症细胞浸润;与模型对照组相比,何首乌5.4 g/kg组血清ALT活力显著升高(P<0.01),IL-1β含量显著升高(P<0.01),SOD和GSH-Px活力显著降低(P<0.01),MDA含量显著升高(P<0.01),肝脏切片可见肝细胞肿胀、坏死,并伴有大量炎症细胞浸润;与何首乌5.4 g/kg组相比,蒲参胶囊10.8 g/kg组血清ALT活力显著降低(P<0.01),IL-1β含量明显降低(P<0.01),SOD和GSH-Px活力明显升高(P<0.05),MDA含量显著降低(P<0.01),肝脏切片偶见炎症细胞浸润,无其他肝组织病变;代谢组学结果显示,模型对照组、何首乌5.4 g/kg组和蒲参胶囊10.8 g/kg组鉴定出共有差异代谢物35个,包含溶血性磷脂酰胆碱、LysoPC、磷脂酰乙醇胺、磷脂酰丝氨酸、等,涉及的关键代谢通路为甘油磷脂代谢。结论:蒲参胶囊可通过调节甘油磷脂代谢改善何首乌在脂多糖诱导下引起的特异质肝损伤。
Objective:To explore the metabolite changes and mechanism of Pushen Capsules in improving heterogeneous liver injury induced by Polygonum multiflorum under the action of lipopolysaccharide.Methods:Ten SD rats were assigned to the blank control group,and the heterogeneous liver injury model was induced by lipopolysaccharide(2.80 mg/g)in 50 rats.The model rats were then divided into a model control group,low-and high-dose Pushen Capsules(5.4 g/kg and 10.8 g/kg)groups,and low-and high-dose P.multiflorum(2.7 and 5.4 g/kg)groups.Rats underwent intragastric administration of corresponding drugs at 15 mL/kg.Five hours later,rats were given lipopolysaccharide solution by tail intravenous injection.Eight hours later,plasma and liver tissues were collected.The activities of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in the plasma,serum levels of interleukin 1β(IL-1β)and interferon gamma(IFN-γ),the activity of superoxide dismutase(SOD),the levels of malondialdehyde(MDA)and glutathione peroxidase(GSH-Px),and pathological changes in liver tissues were detected.Plasma metabolites and metabolic pathways were analyzed by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry(UPLC-QE-Obritrap-MS).Results:Compared with the blank control group,the model control group showed no significant changes in plasma ALT and AST,but slight inflammatory cell infiltration in liver sections.Compared with the model control group,the high-dose P.multiflorum group showed potentiated activity of plasma ALT(P<0.01),increased content of IL-1β(P<0.01),blunted activities of SOD and GSH-Px(P<0.01),and increased content of MDA(P<0.01).Furthermore,hepatocyte swelling,necrosis,and infiltration of inflammatory cells were observed in liver sections.Compared with the high-dose P.multiflorum group,the high-dose Pushen Capsules group showed blunted activity of plasma ALT(P<0.01),decreased content of IL-1β(P<0.01),elevated activities of SOD and GSH-Px(P<0.05),and decreased content of MDA(P<0.01).Inflammatory cell infiltration was occasionally seen in liver sections,while no other liver pathological changes were observed.Metabonomics results indicated that 35 common differential metabolites were identified among the model control group,the high-dose Pushen Capsules group,and the high-dose P.multiflorum group,including lysophosphatidylcholine(LysoPC),phosphatidylethanolamine,and phosphatidyl serine.The key metabolic pathway involved was glycerophospholipid metabolism.Conclusion:Pushen Capsules can improve the heterogeneous liver injury caused by P.multiflorum induced by LPS by regulating the glycerophospholipid metabolism.
作者
张琴
王富江
汪斌
王梅
葛海涛
Zhang Qin;Wang Fujiang;Wang Bin;Wang Mei;Ge Haitao(Nanjing University of Chinese Medicine,Nanjing 210023;Jiangsu Suzhong Pharmaceutical Research Institute Co.,Ltd.,Nanjing 210031)
出处
《中药药理与临床》
CAS
CSCD
北大核心
2022年第5期63-69,共7页
Pharmacology and Clinics of Chinese Materia Medica
基金
中药大品种二次开发项目(编号:SZY01604-PSJ)。
关键词
蒲参胶囊
何首乌
特异质肝损伤
代谢组学
甘油磷脂代谢
Pushen Capsules
Polygonum multiflorum
Heterogeneous liver injury
Metabonomics
Glycerophospholipid metabolism
